It is known that parvoviruses, such as adeno-associated viruses (AAV), disfavor genomes that differ substantially in size from the wild-type genome (e.g., less than about 80 to 85% and greater than about 105 to 107% of wild-type size). This observation also holds true for recombinant parvovirus vectors, where it can limit the size of the transgene and/or regulatory sequences (such as promoters) that can be packaged and efficiently delivered by the vector to target cells.
The present invention overcomes previous shortcomings in the art by providing adenovirus vectors that contain an oversized AAV genome comprising a heterologous nucleotide sequence, and methods of their use